| How
do the bonds cells form with their environments rupture?
What enables some cells to migrate? It is known since
quite a while that cells can have complex mechanical
interactions with their environments. Not only the biochemical
but also the physical properties of their environment
can thus have significant impact on cell behavior and
even gene expression.
Together with fellow researchers
at the University of Washington in Seattle, David
Craig, and the Beckman Institute in Urbana-Champaign
(USA), Klaus Schulten and Mu Gao, ETH Professor Viola
Vogel explored the mechanical interactions between
cells and their extracellular matrices. They wanted
to know how the bond between the proteins which anchor
cells in their environment ruptures if exposed to
tensile forces.
They show in the current issue
of the journal "Structure" that a single
water molecule acts as a gate keeper. It protects
the forcebearing bond between the cell and the extracellular
matrix from attacks by free water molecules and thereby
delays the rupture.
Dynamic picture of the anchoring bond under force
Integrins are transmembrane
proteins which anchor cells to the extracellular matrix
by specific bind to short tri-peptides, i.e. matrix
exposed RGD-peptides. The researchers tested the mechanical
properties of this bond using computer simulations.
They placed the integrin domains
which bind the RGD-peptide into a box filled with
water molecules and applied force between the integrin
and the RGD-peptide. These simulations give the first
dynamic picture how the integrin-RGD complex resists
force-induced dissociation.
Such simulations allow watching
the movement of all water molecules and atoms of the
protein complex under the influence of tensile forces
acting on the integrin-RGD complex. They rev¬ealed
that a single water molecule makes a major contribution
to the mechanical stability of the most critical force-bearing
linkage. The RGD-integrin complex is only formed in
the presence of a doubly charged calcium or manganese
ion. A single water molecule is tightly bound to this
ion and thereby blocks access of free water molecules
to the force bearing bond of the RGD-integrin complex.
Broader significance
While the regulatory functions
of divalent ions in biological processes are well
known, the insights into the dynamic processes of
the RGD-integrin rupture described in the current
issue of “Structure” provide for the first time a
structural basis how the bond between cells and their
environments is stabilized mechanically. Such dynamic
insights might have broader implications. This includes
the development of new drugs or for understanding
the processes how cells attach to and detach from
the surrounding tissue, how they migrate and – in
case of cancer – how they are stimulated to form new
blood vessels.
Notes
Since April 2004, Viola Vogel is a Professor in the
Department of Materials heading the Laboratory for
Biologically Oriented Materials at the Swiss Federal
Institute of Technology (ETH) in Zurich. Part of the
research on integrins she did as head of the Center
for Nanotechnology at Washington University.
Reference URL
http://fm-eth.ethz.ch/eth/media/FMPro?-db=pressemitteilungen.fp5&-format=pr_detail_de.html&-lay=html&-op=eq&pr_id=2004-67&-find
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